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INTRODUCTION: To verify the value of the pathological criteria for additional treatment in locally resected pT1 colorectal carcinoma (CRC) which have been used in the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines since 2009. METHODS: We enrolled 4,667 patients with pT1 CRC treated at 27 institutions between July 2009 and December 2016 (1,257 patients with local resection alone [group A], 1,512 patients with additional surgery after local resection [group B], and 1,898 patients with surgery alone [group C]). All 5 factors of the JSCCR guidelines (submucosal resection margin, tumor histologic grade, submucosal invasion depth, lymphovascular invasion, and tumor budding) for lymph node metastasis (LNM) had been diagnosed prospectively. RESULTS: Any of the risk factors were present in 3,751 patients. The LNM incidence was 10.4% (95% confidence interval 9.4-11.5) in group B/C patients with risk factors, whereas it was 1.8% (95% confidence interval 0.4-5.3) in those without risk factors ( P < 0.01). In group A, the incidence of recurrence was 3.6% in patients with risk factors, but it was only 0.4% in patients without risk factors ( P < 0.01). The disease-free survival rate of group A patients classified as risk positive was significantly worse than those of groups B and C patients. However, the 5-year disease-free survival rate in group A patients with no risk was 99.6%. DISCUSSION: Our large-scale real-world multicenter study demonstrated the validity of the JSCCR criteria for pT1 CRC after local resection, especially regarding favorable outcomes in patients with low risk of LNM.
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BACKGROUND: Neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy is a new standard for locally advanced esophageal squamous cell carcinoma. The optimal timing of pegfilgrastim with the DCF regimen to prevent febrile neutropenia (FN) remains controversial. The effectiveness of concomitant pegfilgrastim administration with continuous 5-fluorouracil (5-FU) infusion in the DCF regimen was therefore assessed. METHODS: All patients who received neoadjuvant DCF for esophageal cancer were retrospectively assessed. Patients who had been scheduled to receive pegfilgrastim on days 3-5 (early group) or days 7-9 (regular group) of the DCF regimen were included. Uni- and multivariate analyses were used to assess risk factors for FN. RESULTS: Eighty-eight patients were included in the analysis. The 26 patients in the early group received pegfilgrastim as scheduled. In the 62 patients of the regular group, 51 received pegfilgrastim at a median of 7 days after starting DCF chemotherapy. However, 11 patients in the regular group could not receive pegfilgrastim. Twenty-two patients of the regular group and 2 patients of the early group developed FN after the first session of DCF. Early administration of pegfilgrastim and grade 4 neutropenia were significantly associated with onset of FN, with multivariate analysis identifying early administration of pegfilgrastim as an independent preventive factor and grade 4 neutropenia as a risk factor, after adjusting for sex and age. CONCLUSION: Early pegfilgrastim administration is a safe approach that reduces the incidence of FN in DCF therapy. Using pegfilgrastim with continuous 5-FU infusion in the DCF regimen represents a reasonable option to prevent FN.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Filgrastim , Neutropenia , Polietilenglicoles , Humanos , Cisplatino , Docetaxel , Neoplasias Esofágicas/patología , Fluorouracilo , Terapia Neoadyuvante , Estudios Retrospectivos , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neutropenia/inducido químicamente , Neutropenia/tratamiento farmacológico , Neutropenia/prevención & controlRESUMEN
BACKGROUND AND AIMS: Since 2009, the Japanese Society for Cancer of the Colon and Rectum guidelines have recommended that tumor budding and submucosal invasion depth, in addition to lymphovascular invasion and tumor grade, be included as risk factors for lymph node metastasis (LNM) in patients with T1 colorectal cancer (CRC). In this study, a novel nomogram was developed and validated by usirge-scale, real-world data, including the Japanese Society for Cancer of the Colon and Rectum risk factors, to accurately evaluate the risk of LNM in T1 CRC. METHODS: Data from 4673 patients with T1 CRC treated at 27 high-volume institutions between 2009 and 2016 were analyzed for LNM risk. To prepare a nonrandom split sample, the total cohort was divided into development and validation cohorts. Pathologic findings were extracted from the medical records of each participating institution. The discrimination ability was measured by using the concordance index, and the variability in each prediction was evaluated by using calibration curves. RESULTS: Six independent risk factors for LNM, including submucosal invasion depth and tumor budding, were identified in the development cohort and entered into a nomogram. The concordance index was .784 for the clinical calculator in the development cohort and .790 in the validation cohort. The calibration curve approached the 45-degree diagonal in the validation cohort. CONCLUSIONS: This is the first nomogram to include submucosal invasion depth and tumor budding for use in routine pathologic diagnosis based on data from a nationwide multi-institutional study. This nomogram, developed with real-world data, should improve decision-making for an appropriate treatment strategy for T1 CRC.
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Neoplasias del Colon , Neoplasias Colorrectales , Humanos , Nomogramas , Metástasis Linfática , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/patología , Invasividad Neoplásica/patologíaRESUMEN
INTRODUCTION: Lubiprostone, a chloride channel activator, is said to reduce epithelial permeability. However, whether lubiprostone has a direct effect on the epithelial barrier function and how it modulates the intestinal barrier function remain unknown. Therefore, the effects of lubiprostone on intestinal barrier function were evaluated in vitro. METHODS: Caco-2 cells were used to assess the intestinal barrier function. To examine the expression of claudins, immunoblotting was performed with specific antibodies. The effects of lubiprostone on cytokines (IFNγ, IL-6, and IL-1ß) and aspirin-induced epithelial barrier disruption were assessed by transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC) labeled-dextran permeability. RESULTS: IFNγ, IL-6, IL-1ß, and aspirin significantly decreased TEER and increased epithelial permeability. Lubiprostone significantly improved the IFNγ-induced decrease in TEER in a dose-dependent manner. Lubiprostone significantly reduced the IFNγ-induced increase in FITC labeled-dextran permeability. The changes induced by IL-6, IL-1ß, and aspirin were not affected by lubiprostone. The expression of claudin-1, but not claudin-3, claudin-4, occludin, and ZO-1 was significantly increased by lubiprostone. CONCLUSION: Lubiprostone significantly improved the IFNγ-induced decrease in TEER and increase in FITC labeled-dextran permeability. Lubiprostone increased the expression of claudin-1, and this increase may be related to the effect of lubiprostone on the epithelial barrier function.
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Claudina-1/metabolismo , Mucosa Intestinal/metabolismo , Lubiprostona/farmacología , Células CACO-2 , Humanos , Interferón gamma/farmacologíaRESUMEN
BACKGROUND/AIMS: Bile acids have recently been associated with the pathogenesis of irritable bowel syndrome (IBS). We therefore evaluated the expression of bile acid receptors in the intestinal mucosa of IBS patients as well as the effects of bile acids on small intestinal epithelial cells. METHODS: Intestinal biopsy specimens were obtained from 15 IBS patients and 15 healthy controls. The effects of bile acid stimulation on trans-epithelial electrical resistance (TEER) and permeability in differentiated Caco-2 cells were measured. Proinflammatory cytokines were measured by enzyme-linked immunosorbent assay. mRNA levels of bile acid receptors, including farnesoid X receptor (FXR), and cytokines were determined by real-time reverse transcription-PCR. Caco-2 cells were pre-incubated with the FXR antagonist guggulsterone. RESULTS: FXR mRNA expression at the terminal ileum was increased in IBS patients. Chenodeoxycholic acid (CDCA) significantly decreased TEER, increased permeability, and increased interleukin-8 (IL-8) release from Caco-2 cells. Pre-incubation with guggulsterone blocked CDCA-mediated IL-8 release; however, the decrease in TEER was not reversed. CDCA-induced IL-6 and IL-8 mRNA levels were blocked by guggulsterone. CDCA increased IL-6, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor release, whereas guggulsterone significantly blocked IL-6 and TNF-α release. CONCLUSIONS: FXR expression was elevated at the terminal ileum in IBS patients. CDCA increased proinflammatory cytokines, while guggulsterone blocked these increases.
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Ácido Quenodesoxicólico/metabolismo , Enterocitos/patología , Síndrome del Colon Irritable/patología , Receptores Citoplasmáticos y Nucleares/metabolismo , Adulto , Anciano , Biopsia , Células CACO-2 , Estudios de Casos y Controles , Enterocitos/inmunología , Enterocitos/metabolismo , Femenino , Voluntarios Sanos , Humanos , Íleon/inmunología , Íleon/metabolismo , Íleon/patología , Interleucina-6/inmunología , Interleucina-6/metabolismo , Interleucina-8/inmunología , Interleucina-8/metabolismo , Síndrome del Colon Irritable/inmunología , Masculino , Persona de Mediana Edad , Permeabilidad , Pregnenodionas/farmacología , ARN Mensajero/aislamiento & purificación , ARN Mensajero/metabolismo , Receptores Citoplasmáticos y Nucleares/antagonistas & inhibidores , Receptores Citoplasmáticos y Nucleares/genética , Factor de Necrosis Tumoral alfa/inmunología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The microbiota in the gut is known to play a pivotal role in host physiology by interacting with the immune and neuroendocrine systems in gastrointestinal (GI) tissues. Glucagon-like peptide 1 (GLP-1), a gut hormone, is involved in metabolism as well as GI motility. We examined how gut microbiota affects the link between GLP-1/GLP-1 receptor (GLP-1R) expression and motility of the GI tract. Germ-free (GF) mice (6 wk old) were orally administered a fecal bacterial suspension prepared from specific pathogen-free (SPF) mice, and then after fecal transplantation (FT) GI tissues were obtained from the GF mice at various time points. The expression of GLP-1 and its receptor was examined by immunohistochemistry, and gastrointestinal transit time (GITT) was measured by administration of carmine red solution. GLP-1 was expressed in endocrine cells in the colonic mucosa, and GLP-1R was expressed in myenteric neural cells throughout the GI wall. GLP-1R-positive cells throughout the GI wall were significantly fewer in GF mice with FT than in GF mice without gut microbiota reconstitution. GITT was significantly shorter in GF mice with FT than in control GF mice without FT and correlated with the number of GLP-1R-positive cells throughout the GI wall. GITT was significantly longer in GF control mice than in SPF mice. When those mice were treated with GLP-1 agonist extendin4, GITT was significantly longer in the GF mice. The gut microbiota may accelerate or at least modify GI motility while suppressing GLP-1R expression in myenteric neural cells throughout the GI tract.NEW & NOTEWORTHY The gut microbiota has been intensively studied, because it plays a pivotal role in various aspects of host physiology. On the other hand, glucagon-like peptide 1 (GLP-1) plays important roles in metabolism as well as gastrointestinal motility. In the present study, we have suggested that the gut microbiota accelerates gastrointestinal motility while suppressing the expression of GLP-1 receptor in myenteric neural cells throughout the gastrointestinal tract. We believe that this article is very timely and suggestive work.
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Microbioma Gastrointestinal/fisiología , Motilidad Gastrointestinal/fisiología , Tracto Gastrointestinal/microbiología , Tránsito Gastrointestinal/fisiología , Péptido 1 Similar al Glucagón/metabolismo , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Animales , Exenatida , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal/efectos de los fármacos , Motilidad Gastrointestinal/efectos de los fármacos , Tránsito Gastrointestinal/efectos de los fármacos , Péptido 1 Similar al Glucagón/genética , Receptor del Péptido 1 Similar al Glucagón/genética , Ratones , Péptidos/farmacología , Ponzoñas/farmacologíaRESUMEN
Regenerating gene (Reg) family proteins, which are classified into four types, commonly act as trophic and/or antiapoptotic factors in gastrointestinal (GI) diseases. However, it remains unclear how these proteins coordinate their similar roles under such pathophysiological conditions. Here, we investigated the interrelationships of Reg family gene expression with mucosal cell proliferation and apoptosis in nonsteroidal anti-inflammatory drug (NSAID)-induced GI injury. GI injury was induced by subcutaneous injection of indomethacin into Reg I knockout (KO) and wild-type (WT) mice, and its severity was scored histopathologically. Temporal changes in the expression of Reg family genes, mucosal proliferation, and apoptosis were evaluated throughout the GI tract by real-time RT-PCR, Ki-67 immunoreactivity, and TUNEL assay, respectively. Reg I, Reg III family, and Reg IV were predominantly expressed in the upper, middle, and lower GI mucosa, respectively. Expression of Reg I and Reg III family genes was upregulated in specific portions of the GI tract after indomethacin treatment. Ki-67-positive epithelial cells were significantly decreased in the gastric and small-intestinal mucosa of Reg I KO mice under normal conditions. After treatment with indomethacin, the number of TUNEL-positive cells was significantly greater throughout the GI mucosa in Reg I KO mice than in WT mice. Expression of Reg I was independent of that of other Reg family genes in, not only normal GI tissues, but also indomethacin-induced GI lesions. Members of the Reg gene family show distinct profiles of expression in the GI tract, and Reg I independently plays a role in protecting the GI mucosa against NSAID-induced injury.
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Antígenos de Neoplasias/metabolismo , Biomarcadores de Tumor/metabolismo , Tracto Gastrointestinal/efectos de los fármacos , Indometacina/farmacología , Lectinas Tipo C/metabolismo , Litostatina/metabolismo , Proteínas de Neoplasias/metabolismo , Animales , Antígenos de Neoplasias/genética , Apoptosis/efectos de los fármacos , Biomarcadores de Tumor/genética , Proliferación Celular/efectos de los fármacos , Colon/efectos de los fármacos , Colon/metabolismo , Colon/patología , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Tracto Gastrointestinal/metabolismo , Tracto Gastrointestinal/patología , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Intestino Delgado/efectos de los fármacos , Intestino Delgado/metabolismo , Intestino Delgado/patología , Lectinas Tipo C/genética , Litostatina/deficiencia , Litostatina/genética , Ratones Endogámicos ICR , Proteínas de Neoplasias/genética , Proteínas Asociadas a Pancreatitis , Factores de TiempoRESUMEN
BACKGROUND: Cancer-associated fibroblasts (CAFs), which reside around tumor cells, are suggested to play a pivotal role in tumor progression. Here we performed microarray analyses to compare gene expression profiles between CAFs and non-cancerous gastric fibroblasts (NGFs) from a patient with gastric cancer and found that fibroblast growth factor 9 (FGF9) was a novel growth factor overexpressed in CAFs. We then examined the biological effects of FGF9 during progression of gastric cancer. METHODS: Expression of FGF9 in CAFs and NGFs, and their secreted products, were examined by Western blotting. The effects of FGF9 on AGS and MKN28 gastric cancer cells in terms of proliferation, invasion and anti-apoptosis were assessed by WST-1 assay, invasion chamber assay and FACS, respectively. Furthermore, the intracellular signaling by which FGF9 exerts its biological roles was examined in vitro. RESULTS: FGF9 was strongly expressed in CAFs in comparison with NGFs, being compatible with microarray data indicating that FGF9 was a novel growth factor overexpressed in CAFs. Treatment with FGF9 promoted invasion and anti-apoptosis through activation of the ERK and Akt signaling pathways in AGS and MKN28 cells, whereas these effects were attenuated by treatment with anti-FGF9 neutralizing antibody. In addition, FGF9 treatment significantly enhanced the expression of matrix metalloproteinase 7 (MMP7) in both cell lines. CONCLUSIONS: FGF9 is a possible mediator secreted by CAFs that promotes the anti-apoptosis and invasive capability of gastric cancer cells.
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Apoptosis/genética , Factor 9 de Crecimiento de Fibroblastos/biosíntesis , Metaloproteinasa 7 de la Matriz/biosíntesis , Neoplasias Gástricas/genética , Anticuerpos Neutralizantes/administración & dosificación , Apoptosis/efectos de los fármacos , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Factor 9 de Crecimiento de Fibroblastos/administración & dosificación , Factor 9 de Crecimiento de Fibroblastos/genética , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Metaloproteinasa 7 de la Matriz/genética , Invasividad Neoplásica/genética , Transducción de Señal/genética , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patologíaRESUMEN
Diarrhea-predominant irritable bowel syndrome (IBS-D)-like symptoms are distressing for patients with quiescent Crohn's disease (qCD) and worsen their quality of life. In the present study, we assessed the effect of the probiotic Bifidobacterium bifidum G9-1 (BBG9-1) on the intestinal environment and clinical features in patients with qCD. Eleven patients with qCD, who met the Rome III diagnostic criteria for IBS-D, received BBG9-1 (24 mg) orally three times daily for 4 weeks. Indices of the intestinal environment (fecal calprotectin level and gut microbiome) and clinical features (CD/IBS-related symptoms, quality of life and stool irregularities) were evaluated before and after treatment. Treatment with BBG9-1 tended to reduce the IBS severity index in the studied patients (p = 0.07). Among gastrointestinal symptoms, abdominal pain and dyspepsia tended to be improved by the BBG9-1 treatment (p = 0.07 and p = 0.07, respectively), and IBD-related QOL showed a significant improvement (p = 0.007). With regard to mental status, the patient anxiety score was significantly lower at the endpoint of BBG9-1 treatment than at the baseline (p = 0.03). Although BBG9-1 treatment did not affect the fecal calprotectin level, it suppressed the serum MCP-1 level significantly and increased the abundance of intestinal Bacteroides in the study patients. The probiotic BBG9-1 is able to improve IBD-related QOL with a reduction of anxiety score in patients with quiescent CD and IBS-D-like symptoms.
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We report a 58-year-old male with a histopathologically proven grade 2 (G2) pancreatic neuroendocrine neoplasm and multiple abdominal node metastases by use of a laparoscopic pancreatic body and tail resection procedure, plus abdominal lymph node dissection. A primary pancreatic tail neuroendocrine tumor sized 20 × 25 mm was detected by contrast-enhanced computed tomography, somatostatin receptor scintigraphy (SRS), and fluorodeoxyglucose positron emission tomography (FDG-PET) examinations and pathologically diagnosed as a pancreatic neuroendocrine tumor (PNET, G2) based on positive immunostaining for somatostatin receptor (SSTR) type 2. Of three metastatic histopathological lymph nodes, two measured 18 × 21 and 10 × 12 mm, respectively, with whole strong SSTR immunostaining showing moderate uptake in SRS findings, whereas the other node, sized 8 × 10 mm, had strong SSTR immunostaining only in a small 6 × 6-mm-sized portion and showed no uptake in SRS findings, likely because of the limited spatial resolution of scintigraphy. On the other hand, only the largest node (18 × 21 mm) was visualized by FDG-PET. SRS may be useful for metastatic lymph node diagnosis based on SSTR immunostaining, though a disadvantage is the spatial resolution limitation.
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BACKGROUND: Serrated polyposis syndrome (SPS), a type of colorectal polyposis characterized by multiple serrated polyps, is associated with a high risk of colorectal carcinoma (CRC). This study aimed to clarify the clinicopathological characteristics of SPS in Japan. METHODS: We investigated the clinicopathological characteristics of patients with SPS from the "Multicenter Study on Clinicopathological Characteristics of SPS (UMIN 000032138)" by the Colorectal Serrated Polyposis Syndrome (SPS) Study Group. In this study, patients were diagnosed with SPS based on the 2019 World Health Organization (WHO) SPS diagnostic criteria. RESULTS: Ninety-four patients were diagnosed with SPS in 10 institutions between January 2001 and December 2017. The mean number (± standard deviation [SD]) of resected lesions per patient was 11.3 ± 13.8. The mean age at diagnosis of SPS was 63.3 ± 11.6 years, and 58 patients (61.7%) were male. Eighty-seven (92.6%) and 16 (17.0%) patients satisfied WHO diagnostic criteria I and II, respectively. Nine patients (9.6%) satisfied both criteria I and II. Carcinoma (T1-T4) were observed in 21 patients (22.3%) and 24 lesions. Of the 21 patients with CRC, 19 (90.4%) satisfied diagnostic criterion I, 1 (4.8%) satisfied diagnostic criterion II, and 1 (4.8%) satisfied diagnostic criteria I and II. There was no notable difference in the prevalence of CRC among patients who met diagnostic criterion I, II, and both I and II. CONCLUSIONS: Patients with SPS have a high risk of CRC and should undergo regular surveillance colonoscopy. Raising awareness of this syndrome is crucial.
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Poliposis Adenomatosa del Colon , Pólipos del Colon , Neoplasias Colorrectales , Poliposis Intestinal , Poliposis Adenomatosa del Colon/diagnóstico , Poliposis Adenomatosa del Colon/epidemiología , Poliposis Adenomatosa del Colon/cirugía , Pólipos del Colon/diagnóstico , Pólipos del Colon/epidemiología , Pólipos del Colon/cirugía , Colonoscopía/métodos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Femenino , Humanos , Poliposis Intestinal/diagnóstico , Poliposis Intestinal/epidemiología , Japón/epidemiología , Masculino , SíndromeRESUMEN
A predictive marker for the development of synchronous/metachronous gastric cancer (GC) would be highly desirable in order to establish an effective strategy for endoscopic surveillance. Herein, we examine the significance of gastric xanthelasma (GX) and molecular abnormalities for the prediction of synchronous/metachronous GC. Patients (n = 115) were followed up (range, 12-122; median, 55 months) in whom the presence of GX and molecular alterations, including microsatellite instability (MSI) and methylation of human mutL homolog 1 (hMLH1), cyclin-dependent kinase inhibitor 2A (CDKN2A) and adenomatous polyposis coli (APC) genes, had been confirmed in non-neoplastic gastric mucosa when undergoing endoscopic submucosal dissection (ESD) for early GC. At the start of surveillance, the numbers of positive subjects were as follows: GX, 59 (51.3%); MSI, 48 (41.7%); hMLH1, 37 (32.2%); CDKN2A, 7 (6.1%); APC, 18 (15.7%). After ESD treatment, synchronous/metachronous GCs occurred in patients with the following positive factors: GX, 16 (27.1%); MSI, 7 (14.6%); hMLH1, 6 (16.2%); CDKN2A, 3 (42.9%); APC, 3 (16.7%). The presence of GX had no significant relationship to positivity for MSI or methylation of hMLH1, CDKN2A or APC. GX was significantly (p = 0.0059) and independently (hazard ratio, 3.275; 95% confidence interval, 1.134-9.346) predictive for the development of synchronous/metachronous GC, whereas those genetic alterations were not predictive. GX is a simple and powerful marker for predicting the development of synchronous or metachronous GC.
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BACKGROUND: The frequency of delayed bleeding after colorectal polypectomy has been reported as 0.6-2.8%. With the increasing performance of polypectomy under continuous use of antithrombotic agents, care is required regarding delayed post-polypectomy bleeding (DPPB). Better instruction to educate endoscopists is therefore needed. We aimed to evaluate the effect of instruction and factors associated with delayed bleeding after endoscopic colorectal polyp resection. METHODS: This single-center, retrospective study was performed to assess instruction in checking complete hemostasis and risk factors for onset of DPPB. The incidence of delayed bleeding, comorbidities, and medications were evaluated from medical records. Characteristics of historical control patients and patients after instruction were compared. RESULTS: A total of 3318 polyps in 1002 patients were evaluated. The control group comprised 1479 polyps in 458 patients and the after-instruction group comprised 1839 polyps in 544 patients. DPPB occurred in 1.1% of polyps in control, and 0.4% in after-instruction. Instruction significantly decreased delayed bleeding, particularly in cases with antithrombotic agents. Hot polypectomy, clip placement, and use of antithrombotic agents were significant independent risk factors for DPPB even after instruction. CONCLUSION: The rate of delayed bleeding significantly decreased after instruction to check for complete hemostasis. Even after instruction, delayed bleeding can still occur in cases with antithrombotic agents or hot polypectomy.
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Serotonin (5hydroxytryptamine; 5HT) may be a key player in gastrointestinal (GI) motility and the GI immune system. In the present study, the effect of gut microbiota on the association between GI motility, and 5HT expression and macrophage abundance in the GI tract was examined. Germfree (GF) mice (6 weeks old) were orally administered a fecal bacterial suspension prepared from specific pathogenfree mice and their GI tissues were evaluated 4 weeks later. The expression of 5HT and mannose receptor (MR) was examined by immunohistochemistry, and GI transit time (GITT) was measured by administration of carmine red solution. The numbers of 5HTpositive endocrine cells and muscularis MRpositive macrophages were significantly increased in the upper GI and colon of GF mice subjected to fecal transplantation (FT) compared with control GF mice without FT. GITT was significantly decreased in GF mice subjected to FT compared with GF mice without FT, and negatively correlated with the numbers of 5HTpositive cells in the upper GI and muscularis MRpositive macrophages throughout the GI tract. The numbers of 5HTpositive endocrine cells and muscularis MRpositive macrophages were significantly correlated throughout the GI tract. The present results suggest that the gut microbiota is involved in the association between accelerated GI motility and induction of the 5HT/muscularis MRpositive macrophage axis in the GI tract.
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Microbioma Gastrointestinal , Motilidad Gastrointestinal , Tracto Gastrointestinal/microbiología , Tracto Gastrointestinal/fisiología , Macrófagos/metabolismo , Serotonina/metabolismo , Animales , Trasplante de Microbiota Fecal , Tracto Gastrointestinal/citología , Vida Libre de Gérmenes , Mucosa Intestinal/metabolismo , Lectinas Tipo C/metabolismo , Masculino , Receptor de Manosa , Lectinas de Unión a Manosa/metabolismo , Ratones Endogámicos ICR , Especificidad de Órganos , Receptores de Superficie Celular/metabolismo , Factores de TiempoRESUMEN
BACKGROUND: Although Helicobacter pylori (H. pylori) infection is closely associated with the development of peptic ulcer, its involvement in pathophysiology in the lower intestinal tract and gastrointestinal (GI) motility remains unclear. Glucagon-like peptide-1 (GLP-1) is a gut hormone produced in the lower intestinal tract and involved in GI motility. Here, we investigated the effect of H. pylori infection on the link between GLP-1 expression and motility of the GI tract. METHODS: C57BL/6 mice were inoculated with a H. pylori strain. Twelve weeks later, the H. pylori-infected mice underwent H. pylori eradication treatment. GI tissues were obtained from the mice at various time intervals, and evaluated for the severity of gastric inflammatory cell infiltration and immunohistochemical expression of GLP-1 and PAX6 in the colonic mucosa. Gastrointestinal transit time (GITT) was measured by administration of carmine-red solution. RESULTS: GLP-1 was expressed in the endocrine cells of the colonic mucosa, and PAX6 immunoreactivity was co-localized in such cells. The numbers of GLP-1- and PAX6-positive cells in the colon were significantly increased at 12 weeks after H. pylori infection and showed a positive correlation with each other. The GITT was significantly longer in H. pylori-infected mice than in non-infected controls and showed a positive correlation with GLP-1 expression. When H. pylori-infected mice underwent H. pylori eradication, GITT and PAX6/GLP-1 expression did not differ significantly from those in untreated H. pylori-infected mice. CONCLUSIONS: H. pylori infection may impair GI motility by enhancing the colonic GLP-1/PAX6 expression.
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Motilidad Gastrointestinal/fisiología , Péptido 1 Similar al Glucagón/metabolismo , Infecciones por Helicobacter/metabolismo , Animales , Colon/metabolismo , Colon/patología , Femenino , Infecciones por Helicobacter/fisiopatología , Helicobacter pylori/patogenicidad , Ratones Endogámicos C57BL , Factor de Transcripción PAX6/metabolismoRESUMEN
We have recently shown that loss of the regenerating gene (Reg) I causes susceptibility to nonsteroidal anti-inflammatory drug-induced gastrointestinal damage. However, the mechanism by which Reg I plays a protective role against this pathophysiological condition is unclear. Here, we investigated whether Reg I plays roles in the induction of tight junction proteins and mucosal barrier function in the small intestine. The small-intestinal permeability was evaluated in Reg I-deficient mice by FITC-dextran and transepithelial electrical resistance (TEER) assay. The effect of REG Iα on TEER, claudins expression, and intracellular signaling was examined using Caco2 cells in vitro. Small-intestinal expression of claudins 3 and 4 was investigated in Reg I-deficient mice in vivo. REG I deficiency significantly decreased the expression of claudin 3 in the small-intestinal epithelium. When mice were treated with indomethacin, the serum level of FITC-dextran in Reg I knockout mice was significantly higher than that in wild-type (WT) mice. The level of small-intestinal TEER was significantly decreased in Reg I knockout mice compared with WT mice under normal condition. REG Iα stimulation significantly enhanced the level of TEER in Caco2 cells. Treatment with REG Iα enhanced the expression of claudins 3 and 4 and promoted Sp1, Akt, and ERK phosphorylation in Caco2 cells, whereas these effects were attenuated by treatment with anti-REG Iα antibody. Reg I may play a role in the maintenance of mucosal barrier function by inducing tight junction proteins such as claudins 3 and 4.
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Claudinas/metabolismo , Intestino Delgado/metabolismo , Litostatina/metabolismo , Animales , Células CACO-2 , Permeabilidad de la Membrana Celular , Impedancia Eléctrica , Células Epiteliales/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Ratones Noqueados , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Factor de Transcripción Sp1/metabolismoRESUMEN
A 35-year-old man was diagnosed to have gastric cancer by endoscopic and histological examinations. Staging laparoscopy detected peritoneal metastasis. Systemic chemotherapy was started, but the patient complained of severe headache. Subsequently, a lumbar puncture demonstrated adenocarcinoma cells in the spinal fluid, suggesting the occurrence of meningeal carcinomatosis (MC) from gastric cancer. MC occurs only rarely in patients with gastric cancer, but the prognosis is invariably poor. However, this patient nevertheless survived for 12 months after receiving intrathecal MTX/Ara-C together with systemic chemotherapy. Therefore, the early detection of meningeal irritation sign and intrathecal chemotherapy might greatly improve the prognosis of gastric cancer patients with MC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinomatosis Meníngea/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Citarabina/administración & dosificación , Resultado Fatal , Cefalea/etiología , Humanos , Inyecciones Espinales , Masculino , Carcinomatosis Meníngea/diagnóstico , Carcinomatosis Meníngea/patología , Metotrexato/administración & dosificación , Pronóstico , Punción Espinal/métodos , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/patologíaRESUMEN
Regenerating gene (REG) Iα is not only overexpressed in a subset of gastric cancers, but also involved in tumor progression. However, the mechanism by which (REG) Iα promotes tumor growth is not fully understood. In the present study, we investigated whether REG Iα plays a role in angiogenesis during the progression of gastric cancers. Expression of REG Iα and its receptor (EXTL3; exostoses like-3) was examined using immunohistochemistry in specimens of human gastric cancer. Microvessel density (MVD) in gastric cancer tissues was evaluated using an image analysis system after CD34 immunostaining. Relationships among clinicopathological features, REG Iα expression and MVD in gastric cancer tissues were analyzed. Effects of REG Iα protein on HUVEC cells in terms of proliferation and anti-apoptosis were assessed by WST-1 assay and FACS, respectively. Furthermore, the intracellular signaling by which REG Iα exerts its biological roles was examined in vitro. REG Iα expression was significantly related to lymph node metastasis and its receptor EXTL3 was ubiquitously expressed in not only the tumor cells, but also the tumor vessel cells in the gastric cancer tissues. MVD was significantly higher in gastric cancers that were REG Iα-positive than in those that were negative. Treatment with REG Iα protein promoted growth and anti-apoptosis through activation of the ERK and Akt signaling pathways in HUVEC cells, whereas these effects were attenuated by treatment with anti-REG Iα -antibody. REG Iα protein may play a role in angiogenesis during progression of gastric cancer.